Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact
cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease
pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an
exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor
associations in ME/CFS compared with multiple sclerosis participants and healthy controls.
Methods: This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55
with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from
primary and secondary health services. Data were collected from participants using a standardised written
questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to
disease onset).
Results: A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were
the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41,
P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher
risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P <
0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having
lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were
associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness
(OR = 6.1, P = 0.001).
Conclusions: Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and
MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations
between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent
infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to
investigate, our findings are consistent with the increasing body of evidence that has been published about the
potential role of infections in the pathogenesis of ME/CFS, including common colds/flu